Matches in SemOpenAlex for { <https://semopenalex.org/work/W2105610478> ?p ?o ?g. }
- W2105610478 endingPage "548" @default.
- W2105610478 startingPage "535" @default.
- W2105610478 abstract "ABSTRACT Hypersecretion of acid hydrolases is a hallmark feature of mucolipidosis II (MLII), a lysosomal storage disease caused by loss of carbohydrate‐dependent lysosomal targeting. Inappropriate extracellular action of these hydrolases is proposed to contribute to skeletal pathogenesis, but the mechanisms that connect hydrolase activity to the onset of disease phenotypes remain poorly understood. Here we link extracellular cathepsin K activity to abnormal bone and cartilage development in MLII animals by demonstrating that it disrupts the balance of TGFß‐related signaling during chondrogenesis. TGFß‐like Smad2,3 signals are elevated and BMP‐like Smad1,5,8 signals reduced in both feline and zebrafish MLII chondrocytes and osteoblasts, maintaining these cells in an immature state. Reducing either cathepsin K activity or expression of the transcriptional regulator Sox9a in MLII zebrafish significantly improved phenotypes. We further identify components of the large latent TGFß complex as novel targets of cathepsin K at neutral pH, providing a possible mechanism for enhanced Smad2,3 activation in vivo. These findings highlight the complexity of the skeletal disease associated with MLII and bring new insight to the role of secreted cathepsin proteases in cartilage development and growth factor regulation. © 2015 American Society for Bone and Mineral Research." @default.
- W2105610478 created "2016-06-24" @default.
- W2105610478 creator A5022249737 @default.
- W2105610478 creator A5029464451 @default.
- W2105610478 creator A5030151382 @default.
- W2105610478 creator A5034038476 @default.
- W2105610478 creator A5066099848 @default.
- W2105610478 creator A5081740669 @default.
- W2105610478 creator A5084119001 @default.
- W2105610478 creator A5089305746 @default.
- W2105610478 date "2015-10-13" @default.
- W2105610478 modified "2023-10-16" @default.
- W2105610478 title "Cathepsin-Mediated Alterations in TGFß-Related Signaling Underlie Disrupted Cartilage and Bone Maturation Associated With Impaired Lysosomal Targeting" @default.
- W2105610478 cites W122315776 @default.
- W2105610478 cites W1545682756 @default.
- W2105610478 cites W1547454641 @default.
- W2105610478 cites W1566859644 @default.
- W2105610478 cites W1574722884 @default.
- W2105610478 cites W1606568236 @default.
- W2105610478 cites W163466579 @default.
- W2105610478 cites W1964293830 @default.
- W2105610478 cites W1976360222 @default.
- W2105610478 cites W1976781053 @default.
- W2105610478 cites W1983936693 @default.
- W2105610478 cites W1993163303 @default.
- W2105610478 cites W1998008605 @default.
- W2105610478 cites W1998379420 @default.
- W2105610478 cites W2008298886 @default.
- W2105610478 cites W2011966089 @default.
- W2105610478 cites W2013436606 @default.
- W2105610478 cites W2015050458 @default.
- W2105610478 cites W2016034917 @default.
- W2105610478 cites W2018822666 @default.
- W2105610478 cites W2020733002 @default.
- W2105610478 cites W2023431960 @default.
- W2105610478 cites W2024805424 @default.
- W2105610478 cites W2025202177 @default.
- W2105610478 cites W2032266921 @default.
- W2105610478 cites W2033260397 @default.
- W2105610478 cites W2040155058 @default.
- W2105610478 cites W2044482567 @default.
- W2105610478 cites W2053188090 @default.
- W2105610478 cites W2055931397 @default.
- W2105610478 cites W2056317902 @default.
- W2105610478 cites W2058877705 @default.
- W2105610478 cites W2062718003 @default.
- W2105610478 cites W2067393615 @default.
- W2105610478 cites W2067439258 @default.
- W2105610478 cites W2072025455 @default.
- W2105610478 cites W2072378482 @default.
- W2105610478 cites W2081213518 @default.
- W2105610478 cites W2091760375 @default.
- W2105610478 cites W2096492484 @default.
- W2105610478 cites W2099920893 @default.
- W2105610478 cites W2103947324 @default.
- W2105610478 cites W2108274213 @default.
- W2105610478 cites W2109553414 @default.
- W2105610478 cites W2112137534 @default.
- W2105610478 cites W2113762991 @default.
- W2105610478 cites W2121554092 @default.
- W2105610478 cites W2122588714 @default.
- W2105610478 cites W2122947761 @default.
- W2105610478 cites W2125349610 @default.
- W2105610478 cites W2128448507 @default.
- W2105610478 cites W2134859844 @default.
- W2105610478 cites W2136526854 @default.
- W2105610478 cites W2138597978 @default.
- W2105610478 cites W2146765224 @default.
- W2105610478 cites W2152350731 @default.
- W2105610478 cites W2154967508 @default.
- W2105610478 cites W2161629050 @default.
- W2105610478 cites W2161998042 @default.
- W2105610478 cites W2163179326 @default.
- W2105610478 cites W4239370680 @default.
- W2105610478 doi "https://doi.org/10.1002/jbmr.2722" @default.
- W2105610478 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4808492" @default.
- W2105610478 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26404503" @default.
- W2105610478 hasPublicationYear "2015" @default.
- W2105610478 type Work @default.
- W2105610478 sameAs 2105610478 @default.
- W2105610478 citedByCount "16" @default.
- W2105610478 countsByYear W21056104782016 @default.
- W2105610478 countsByYear W21056104782017 @default.
- W2105610478 countsByYear W21056104782018 @default.
- W2105610478 countsByYear W21056104782019 @default.
- W2105610478 countsByYear W21056104782020 @default.
- W2105610478 countsByYear W21056104782021 @default.
- W2105610478 countsByYear W21056104782023 @default.
- W2105610478 crossrefType "journal-article" @default.
- W2105610478 hasAuthorship W2105610478A5022249737 @default.
- W2105610478 hasAuthorship W2105610478A5029464451 @default.
- W2105610478 hasAuthorship W2105610478A5030151382 @default.
- W2105610478 hasAuthorship W2105610478A5034038476 @default.
- W2105610478 hasAuthorship W2105610478A5066099848 @default.
- W2105610478 hasAuthorship W2105610478A5081740669 @default.
- W2105610478 hasAuthorship W2105610478A5084119001 @default.
- W2105610478 hasAuthorship W2105610478A5089305746 @default.
- W2105610478 hasBestOaLocation W21056104781 @default.